Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy

Background: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4+ T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned. Methods: Study within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4+ T-cells per μL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRISFRENCH) or by a clinical IRIS diagnosis of the physician (IRISCLINICAL). The primary outcomes were the association between INI and the occurrence of IRISFRENCH and IRISFRENCH+CLINICAL in multivariable logistic regression. Findings: 672 patients with a median CD4+ T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRISFRENCH as well as IRISFRENCH+CLINICAL (OR 2·43, 95%CI:1·45–4·07, and OR 2·17, 95%CI:1·45–3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRISFRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRISFRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRISFRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p=0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed. Interpretation: In HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters. Funding: Th

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research.</p

Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study)

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe

The importance of registration of sexual orientation and recognition of indicator conditions for an adequate HIV risk-assessment

HIV testing among risk groups and guided by HIV indicator conditions (IC) is widely recommended by European guidelines. In this study we investigated how these strategies are used by general practitioners (GP) and in other healthcare settings. The objectives of our study were to describe: 1) the proportion of consultations in primary care and other healthcare settings in the five years prior to diagnosis; 2) patient and GP perspectives on the primary healthcare providers' awareness and registration of sexual orientation and ethnicity in the electronic medical record (EMR); and 3) the proportion of HIV-infected patients who had been diagnosed with an IC prior to HIV diagnosis. A survey study (2014-2016) was conducted among newly diagnosed HIV-infected patients presenting at two HIV outpatient clinics in Amsterdam. We collected information on the number of consultations and extent of HIV testing in healthcare settings in the 5 years prior to HIV diagnosis; on patient and GP perspectives on the primary healthcare providers' awareness of sexual orientation and ethnicity; and on preselected ICs and symptoms of acute HIV infection prior to diagnosis. GPs were also approached for further information. In the 5 years prior to HIV diagnosis, 82.9% of the 111 patients had one or more consultations with their GP, but only 34.8% had one or more HIV tests performed in general practice during this period. In more than 50% of cases the patients took the initiative for the positive HIV test. GPs stated that they were aware of the sexual orientation of 59.6% of their patients who were men who have sex with men (MSM); however, sexual orientation was only documented in the EMR in 34.0% of these cases. GPs also reported that they were aware that a patient was from an HIV endemic country in more than half of the cases. GPs diagnosed 48.3% of all ICs and 39.5% of this group was offered an HIV test at that time. Documentation of sexual orientation and ethnicity, and IC-guided testing by GPs could be the starting point for more proactive provider-initiated HIV testin

Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors

Background: Prolonged exposure to protease inhibitor (PI)-, but not non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing combination antiretroviral therapy (CART) has been associated with an increased cardiovascular risk, partly explained by the different effects of these drugs on plasma lipids. Most markedly, NNRTIs have been associated with increases in high density lipoprotein cholesterol (HDL-C), which may be atheroprotective. Methods: In a cross-sectional study we investigated the impact of PI-vs. NNRTI-based CART in 130 HIV-1-infected patients with plasma virus suppressed to below the limit of detection, whom had been continuously exposed for at least 2 years to either one of such regimens, but not both. Carotid intima-media thickness (C-IMT) and fasting metabolic parameters were measured. Results: Mean (S.D.) C-IMT in patients treated with PI-based CART was 0.81 (+/- 0.17) mm as compared to 0.71 ( 0.14) mm in NNRTI treated patients (p=0.0003). HDL-C and apolipoprotein A-I (apoA-I) levels were higher in the NNRTI than in the PI group (1.39 mmol/L vs. 1.03 mmol/L; p <0.0001, and 1.44 mmol/L vs. 1.33 mmol/L; p=0.0008, respectively). Framingham Risk Score, body mass index, duration of CARE, and use of PI-based CART were positively correlated with C-IMT whereas HDL-C and apoA-I were inversely correlated with C-IMT. Conclusions: Treatment of HIV-1-infected patients for 2 years or more with PI-based compared to NNRTI-based CART is associated with greater C-IMT, consistent with the reported higher risk of C VD in patients using PI. However, this difference seems not fully explained by a more favorable impact of NNRTI-based CART on HDL-C and apoA-I levels. (C) 2008 Elsevier Ireland Ltd. All rights reserve

Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study)

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe

Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: The ATHENA cohort study

Background. Recommendations that nevirapine (NVP) should be avoided in female individuals with CD4 cell counts >250 cells/μL and in male individuals with CD4 cell counts >400 cells/μL are based on findings in treatment-naive patients. It is unclear whether these guidelines also apply to treatment-experienced patients switching to NVP-based combination therapy. Methods. Patients in the ATHENA cohort study who had used NVP-based combination therapy were included. We identified patients who discontinued NVP-based combination therapy because of hypersensitivity reactions (HSRs; rash and/or hepatotoxicity) within 18 weeks after starting such therapy. We grouped patients according to their CD4 cell count at the start of NVP-based combination therapy (current CD4 cell count) as having a high CD4 cell count (for female patients, >250 cells/μL; for male patients, >400 cells/μL) or a low CD4 cell count. Treatment-experienced patients were further subdivided according to the

L'ordinamento giuridico italiano nello "spazio di libertà. sicurezza e giustizia"

Una delle più significative novità introdotte con il Trattato di Lisbona è stata quella di aver mutato profondamente l’assetto precedente dello spazio di libertà sicurezza e giustizia. Ciò ha determinato un sostanziale cambiamento della tipologia di atti normativi che dal 2009 in poi sono emanati in questa materia ed anche gli atti precedenti hanno acquistato dal 1° dicembre 2014 piena efficacia, con tutela giurisdizionale della Corte di giustizia e la possibilità di procedimento d’infrazione da parte della Commissione. La chiave di lettura della ricerca è stata quella di verificare l’evoluzione che hanno avuto le fonti europee e quelle interne in tema di cooperazione giudiziaria e di polizia, analizzando quelle sfere di criminalità particolarmente gravi con dimensione transnazionale che richiedono non solo una maggiore collaborazione fra gli Stati, ma l’introduzione di norme minime unitarie. I settori in cui è maggiore l’interesse europeo ad una cooperazione ed armonizzazione delle norme penali e che il Trattato di Lisbona conferisce alla competenza del Parlamento e del Consiglio dell’Unione sono la lotta al terrorismo, la tratta degli esseri umani, il traffico illecito degli stupefacenti, il riciclaggio di denaro, la criminalità informatica ed organizzata. Tutti questi temi sono stati analiticamente studiati in questa ricerca